All animal life starts with the fertilization of an egg. A haploid egg and a haploid sperm fuse and together they form a new genetically unique embryo. But surprisingly, eggs frequently contain an incorrect number of chromosomes. Depending on the age of the woman, 10-50% of eggs are chromosomally abnormal. This high percentage of abnormal eggs results from chromosome segregation errors during oocyte maturation, the process by which a diploid oocyte matures into a haploid egg. Thus, errors during meiosis in human oocytes are the most common cause of pregnancy losses and contribute to approximately 95% of human aneuploidy such as Down’s syndrome. Surprisingly, we still know very little about how mammalian oocytes mature into eggs, and it is still unclear why chromosome segregation during meiosis is so much more error-prone than during mitosis.My proposal combines three innovative and complementary approaches towards understanding how homologous chromosomes are segregated and why oocyte maturation in mammals is so error-prone. Specifically, we will work towards the following three aims: 1. We will complete the first large scale screen for genes required for accurate progression through meiosis in mammalian oocytes and characterize the function of a few selected genes in detail. 2. We will analyse meiosis and investigate potential causes of chromosome segregation errors directly in live human oocytes. 3. We will study the function of an F-actin spindle and a chromosome-associated myosin that might be required for chromosome segregation in mammalian oocytes.Because errors during oocyte maturation lead to pregnancy loss, birth defects and infertility, this work will not only provide important insights into fundamental cellular mechanisms, but will also have important implications for human health.